Processes for preparing JAK inhibitors and related intermediate compounds
AssigneeIncyte Corporation
InventorJiacheng Zhou
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Abstract
The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.
Claims3
A process of preparing a composition comprising an enantiomeric excess of the (R)-enantiomer of a compound of Formula III′:
- comprising:
- (a) treating a compound of Formula XI′:
- with sodium hydride and 2-(trimethylsilyl)ethoxymethyl chloride to form a compound of Formula X″:
- (b) treating said compound of Formula X″ with a compound of Formula XIII′:
- in the presence of Pd(triphenylphosphine)4, potassium carbonate, and a solvent, to form a compound of Formula XII″:
- (c) reacting said compound of Formula XII″ under deprotection conditions to form a compound of Formula IV″:
- (d) reacting said compound of Formula IV″ with a compound of Formula D-1′:
- under conditions sufficient to form a composition comprising a racemate of a compound of Formula I″:
- (e) passing said composition comprising said racemate of said compound of Formula I″ through a chiral chromatography unit using a mobile phase and collecting a composition comprising an enantiomeric excess of the (R)-enantiomer of said compound of Formula I″;
- and
- (f) reacting said compound of Formula I″ with boron trifluoride diethyl etherate, followed by aqueous ammonium hydroxide to form a composition comprising an enantiomeric excess of the (R)-enantiomer of said compound of Formula III′;
- wherein * is a chiral carbon.
A compound of Formula XII″, which is:
- or a pharmaceutically acceptable salt thereof.
A composition comprising an enantiomeric excess of the (R)-enantiomer of a compound of Formula I″
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.